Methoxy-substituted cyanophenyl ester derivatives of phosphorus acids

ABSTRACT

Methoxy-substituted cyanophenyl ester derivatives of phosphinic, phosphonic, phosphoric, thiophosphinic, thiophosphonic, and thiophosphoric acids having the general formula: ##EQU1## wherein R and R 1  are independently selected from the group consisting of lower alkyl, chloro-substituted lower alkyl, lower alkoxy, phenyl, phenoxy and lower dialkylamido, and X is oxygen or sulfur. The compounds are effective pesticides especially in the control of houseflies, American cockroach, milkweed bug and two-spotted mite. Representative compounds are O-ethyl-O-(2-methoxy-4-cyanophenyl) ethyl phosphonothioate and O,O-dimethyl-O-(2-methoxy-4-cyanophenyl) phosphorothioate.

This application is a continuation-in-part of co-pending applicationSer. No. 328,463, filed Dec. 6, 1963, and now abandoned.

This invention is directed to certain novel phosphorus-containingcompounds, a process for preparing said compounds, and their method ofuse as pest-controlling agents.

The novel compounds are the methoxy-substituted cyanophenyl esterderivatives of phosphinic, phosphonic, phosphoric, thiophosphinic,thiophosphonic, and thiophosphoric acids, which compound may berepresented generically by the following general formula: ##STR1##wherein R and R¹ are independently selected from the group consisting oflower alkyl, chloro-substituted lower alkyl, lower alkoxy, phenyl,phenoxy, and lower dialkylamido, and X is selected from the groupconsisting of oxygen and sulfur. The lower alkyl, chloro-substitutedlower alkyl, and lower alkoxy groups represented by R and R¹, willcontain up to 8 carbon atoms, either in branched or straight chains. Thealkyl portions of the dialkylamido radicals will contain from 1 to 3carbon atoms.

The novel compounds of the present invention are prepared according tothe following general reaction: ##STR2## WHEREIN Hal stand for a halogenselected from chlorine, iodine, and bromine, preferably chlorine,"acceptor" stands for a hydrogen halide acceptor such as a tertiaryamine or the like, and R, R¹, and X are as defined hereinbefore.Reaction is preferably carried out at or slightly above roomtemperature, for example, at a temperature between about 20° and 80° C.,although the reaction is possible at all temperatures between about 0°and 100° C. The hydrogen halide acceptor is useful in preventingpossible side reactions between the product and the halogen acidgenerated in the reaction. In a preferred process for making the novelcompounds of the invention, the reaction is preferably carried out inthe presence of an inert organic solvent such as benzene, dioxime,toluene, and xylene. By a variation of the process, sodium carbonate, orthe like, may be used in place of the hydrogen halide acceptor to removeacid from the reaction matrix.

The preparation of the compound of this invention is illustrated by thefollowing non-limiting examples, many variations of which will occur tothose skilled in the art without departing from the spirit or scopethereof:

EXAMPLE 1 ##STR3##

To 7.5 grams of vanillin nitrile, 6.0 grams of triethylamine and 75 ml.benzene maintained at a temperature of 20° - 30° C. was added 11.4 gramsof (C₄ H(O)₂ P(O)Cl. The reaction matrix was allowed to stir for 48hours, after which time it was filtered and the filtrate was washed. Thefiltrate was then concentrated by evaporation to 60° C. at 1 mm. Hg toyield 12.6 grams (72% of theoretical yield) ofO,O-dibutyl-O-(2-methoxy-4-cyanophenyl) phosphate, having an index ofrefraction N_(D) ²⁵ = 1.5331.

EXAMPLE 2 ##STR4##

To 8.7 grams of (C₂ H₅ O)₂ P(O)Cl and 20 ml. of benzene was addeddropwise, at 25° C., 7.5 grams of vanillin nitrile and 6.0 grams oftriethylamine and 75 ml. of benzene. After stirring overnight at roomtemperature, the reaction mixture was heated to 60° C. for 1 hour,cooled, filtered, and the filtrate was concentrated by evaporation to60° C. at 1 mm. Hg. The concentrate consisted of 14.0 grams (97% oftheoretical yield) of O,O-diethyl-O-(2-methoxy-4-cyanophenyl) phosphate,having an index of refraction N_(D) ²⁵ = 1.4991. By analysis, theproduct consisted of 10.9% P, 4.1% N, and 0.3% Cl, compared to thetheoretical values of 10.9% P, 4.1% N, and 0.0% Cl for the compound ofthe formula shown immediately above. EXAMPLE 3 ##STR5##

To 5.0 grams of vanillin nitrile and 3.7 grams of triethylamine in 75ml. of benzene was added 6.3 grams of (C₂ H₅ O)₂ P(S)Cl and 20 ml. ofbenzene, while maintaining the reaction temperature between 25° and 35°C. The reaction matrix was allowed to stir for one hour at roomtemperature, after which it was heated to 65° C., ± 5° C. for two hours.This reaction was followed by cooling, filtration, and concentration ofthe filter cake by evaporation to 60° C. at 1 mm. Hg. to yield 6.5 grams(65% of theoretical yield) of O,O-diethyl-O-(2-methoxy-4-cyanophenyl)phosphorothioate having an index of refraction N_(D) ²⁵ = 1.5208. Byanalysis, the product was found to contain 10.1% P, 11.3% S, and 3.5% N,compared to the theoretical values of 10.3% P, 10.6% S, and 4.65% N.

EXAMPLE 4 ##STR6##

Using the procedure described in the foregoing example, and analogousstarting materials, a 99 % yield ofO,O-n-propyl-O-(2-methoxy-4-cyanophenyl) phosphorothioate having anindex of refraction N_(D) ²⁵ = 1.5168 was prepared. This productanalyzed as 9.1% P, 9.3% S, and 4.1% N, as compared to the theoreticalvalues of 9.4% P, 9.7% S, and 4.25% N.

EXAMPLE 5 ##STR7##

To 6.0 grams of Na₂ CO₅ and 7.5 grams of vanillin nitrile in acetone wasadded 8.0 grams of (CH₃ 0)₂ P(S)Cl. The reaction mixture was warmed toreflux temperature for five hours, cooled, and then poured into 250 cc.of ice water. The solids were then recovered, filtered and dried toyield 9.3 grams (68% of theoretical yield) ofO,O-dimethyl-O-(2-methoxy-4-cyanophenyl)phosphorothioate. This productwas found to have a melting point at 70° - 75° C. and an analysis of9.8% P, 10.3% S, and 5.5% N, compared to 11.4% P, 11.7% S, and 5.1% N,theoretical.

EXAMPLE 6 ##STR8##

To 7.5 grams of vanillin nitrile and 6.0 grams of triethylamine in 50ml. of benzene was added 7.4 grams of (CH₃) (C₂ H₅ O)P(S)Cl in 10 ml. ofbenzene at 30° to 35° C. The reaction mixture was allowed to stir forone hour longer and then heated for an additional hour at 60° C., afterwhich it was cooled and added to 100 cc. of water to dissolve thetriethylamine hydrochloride. The organic fraction was transferred to aseparatory funnel and washed with 50 ml. of 2% NaCH and 50 ml. of water.The aqueous phase was then counter-washed with 50 cc. of benzene. Thebenzene wash and the product were combined and concentrated byevaporation at 70° C. and 2 mm. Hg to yield 12.0 grams of solids havinga melting point of 95° - 100° C. The solid product was analyzed andfound to be O-ethyl-O-(2-methoxy-4-cyanophenyl) methylphosphonothioate,having an elemental composition of 10.9% P, 10.7% S, and 5.2% N,compared to 11.4% P, 11.8% S, and 5.2% N, theoretical.

Using a procedure substantially in accordance with those described inthe foregoing examples, the following specific compounds were prepared:

EXAMPLE 7 ##STR9## O-ethyl-O-(2-methoxy-4-cyanophenyl)phenylphosphonothioate.

Analysis - Found: 9.1% P; 10.0% S; 4.0% N; Calcd: 9.3% P; 9.6% S; 4.2%N. Yield = 63% of theory.

EXAMPLE 8 ##STR10## O-(2-methoxy-4-cyanophenyl)ethylphenylphosphinothioate.

Analysis - Found: 9.8% P; 10.3% S; 4.0% N; Calcd: 9.8% P; 10.1% S; 4.4%N. Yield = 85% of theory.

EXAMPLE 9 ##STR11## O-ethyl-O-(2-methoxy-4-cyanophenyl)chloromethylphsophonothioate

Analysis - Found: 10.0% P; 10.4% S; 7.7% Cl; 4.1% N; Calcd: 10.2% P;10.5% S; 11.6% Cl; 4.6% N.

EXAMPLE 10 ##STR12## O-propyl-O-(2-methoxy-4-cyanophenyl)chloromethylphosphonothioate

Analysis - Found: 9.3% P; 9.8% S; 12.2% Cl; 4.5% N; Calcd: 9.7% P; 10.0%S; 11.1Cl; 4.4% N. Yield = 84.0% of theory.

EXAMPLE 11 ##STR13## O-(2-methoxy-4-cyanophenyl)dichloromethylphosphinothioate

Yield = 95% of theory.

EXAMPLE 12 ##STR14## O-(2-methoxy-4-cyanophenyl)-N,N-dimethylphenylphosphonamidate

Analysis - Found: 9.4% P; 8.6% N; Calcd: 9.8% P; 8.9% N. Yield = 95.0%of theory.

EXAMPLE 13 ##STR15## O-ethyl-O-(2-methoxy-4-cyanophenyl) ethylphosphonothioate. Melting point 74.5°-76.5° C.

Analysis - Found: 10.80% P; 11.34% S; 4.89% N; Calcd: 10.88% P; 11.23%S; 4.91% N. Yield = 70% of theory.

EXAMPLE 14 ##STR16## O-isobutoxy-O-(2-methoxy-4-cyanophenyl)ethylphosphonothioate. EXAMPLE 15 ##STR17##O-isopropyl-O-(2-methoxy-4-cyanophenyl) methyl phosphonothioate.

The following related compounds can also be prepared by reactionssimilar to those shown in Examples 1 through 6, using the correspondingreactants: ##STR18## O,O-di-i-propyl-O-(2-methoxy-4-cyanophenyl)phosphate ##STR19## O,O-dimethyl-O-(3-methoxy-4-cyanophenyl)phosphorothioate ##STR20## O-ethyl-O-octyl-O-(2-methoxy-5-cyanophenyl)phosphorothioate ##STR21##

O,O-dioctyl-O-(3-cyano-4-methoxyphenyl) phosphate ##STR22##O,O-dimethyl-O-(2-cyano-3-methoxyphenyl) phosphorothioate ##STR23##O-octyl-O-(2-methoxy-4-cyanophenyl) ethylphosphonate ##STR24##O-(2-methoxy-4-cyanophenyl) diphenyl phosphinothioate ##STR25##O,O-diphenyl-O-(2-methoxy-4-cyanophenyl) phosphorothioate ##STR26##O,O-dimethyl-O-(2-cyano-6-methoxyphenyl) phosphonothioate. ##STR27##O-ethyl-O-(2-cyano-6-methoxyphenyl) ethylphosphonothioate ##STR28##O,O-diethyl-O-(2-methoxy-5-cyanophenyl) phosphorothioate ##STR29##O-methyl-O-(2-methoxy-5-cyanophenyl) ethylphosphonate.

The aforesaid compounds have been tested as pesticides by the followingmethods:

Adult houseflies and nymphs of the American cockroach and milkweed bugare caged in cardboard mailing tubes with cellophane bottoms and coarsemesh nylon tops and supplied with food and water. From 10 to 25 insectsare employed per cage, depending on the species.

The candidate compounds are dissolved in 10 ml. of a suitable solvent,usually acetone. Aliquots of the toxicant solutions are suspended inwater containing 0.0175% by volume Sponto 221, an emulsifying agent, andsprayed on the caged insects. The compounds are sprayed with a DeVilbiashandsprayer at 20 psi in a fume hood. Final mortality readings are takenafter seventy-two hours. The two-spotted mite, Tetranychus telarius(Linn.) is screened by using young pinto bean plants in the primary leafstage as the host plant. The plant is dipped in an aqueous suspension ofthe candidate compound and the soil is drenched at a concentration of100 ppm. based on the weight of the soil. Mites are confined to theleaves with small clip cages. Pesticidal activity is illustrated in thefollowing table, wherein the percentage kill among a group of testspecies is reported for a specified percentage concentration of toxicantin aqueous solution. A slanted line is used to separate the percentagekill, shown on the left, and the percentage concentration, shown on theright. The pest species tested are as follows:

    ______________________________________                                        House fly                                                                     Musca domestica                                                                                 (Linn.)                                                     American cockroach                                                            Paraplaneta americana                                                                           (Linn.)                                                     Spotted milkweed bug                                                          Oncopeltus fasciatus                                                                            (Dallas)                                                    Two-spotted mite                                                              Tetranychus telarius                                                                            (Linn.)                                                     ______________________________________                                    

                                      TABLE I                                     __________________________________________________________________________               Compound                                                                      (Example No.)                                                      __________________________________________________________________________               2      5      6      8      10     13                                         %kill/conc.                                                                          %kill/conc.                                                                          %kill/conc.                                                                          %kill/conc.                                                                          %kill/conc.                                                                          %kill/conc.                     __________________________________________________________________________    House Flies                                                                              100/0.1                                                                              100/0.1                                                                              100/0.1                                                                              100/0.1                                                                              100/0.1                                                                              100/0.1                         American Cockroach                                                                       80/0.05                                                                              100/0.01                                                                             100/0.01                                                                              40/0.005                                                                            60/0.05                                                                              --                              Milkweed Bug                                                                             90/0.01                                                                              100/0.01                                                                             100/0.01                                                                             100/0.05                                                                             80/0.05                                                                              50/0.003                        Two-spotted Mite                                                                         50/0.1 25/0.1 100/0.01                                                                             100/0.05                                  

The compounds of Examples 2, 5, 6, 8 and 13, which showed high activityagainst insects, were bioassayed on the house fly according to thefollowing procedure: Cages such as those described for the insecticidescreening tests above were used. Acetone solutions of the candidatematerials were prepared and measured aliquots were placed in pyrex Petridishes having a surface area of 18.8 sq. ccm. One ml. of a suspension ofpeanut oil and acetone was added as a filming agent. The solvent wasevaporated by air-drying and groups of 25 female flies, 3 to 5 days old,were exposed to the residues on the Petri dishes which were placed inthe cages. Final mortality readings were taken 48 hours after initiationof the test. The results of these tests are presented in the followingtable wherein the percentage kill is shown on the left of the slantedline, and the amount of toxicant is shown on the right.

                  TABLE II                                                        ______________________________________                                                                                      1                               Compound                                                                      (Example No.)                                                                             %kill/g.   %kill/g.   %kill/g.                                    ______________________________________                                        2           96/5       4/1                                                    5           100/10     68/5       8/1                                         6           100/10     88/5       8/1                                         8           100/5      0/1                                                    13          100/10      92/2.5    4/1                                         ______________________________________                                    

Compound number 5 and compound number 13 exhibited unusual activityagainst lygus bug (Lygus hesperus (Knight)), Compound number 5 has anLD-50 value of 0.0008 percent toward lygus bug and compound number 13has an LD-50 value of 0.0003 percent.

Where used herein, the term "pesticide" is intended in the restrictedsense generally recognized in the art as applying to the lower forms oflife customarily controlled by chemical means and excluding the higheranimals, the vertabrates, e.g., rodents, birds, and larger forms whichare more commonly controlled by mechanical means, such as traps. Itwill, however, be apparent to one skilled in the art that the toxicactivity of the new compounds with various pest species is indicative ofactivity with species and orders not specifically shown.

Although the above pesticidal tests were accomplished with aqueousdispersion, the toxic compounds may also be used in the form ofsolutions (aqueous) when appreciably water-soluble, non-aqueoussolutions, wettable powders, vapors, and dusts, as may be best suited tothe conditions of use.

We claim:
 1. A compound having the formula: ##EQU2##where R and R¹ aremembers independently selected from the group consisting of lower alkyl,chloro-substituted lower alkyl, lower alkoxy, phenyl, and phenoxy; and Xis a member selected from the group consisting of oxygen and sulfur. 2.A compound having the formula: ##STR30##wherein R and R¹ are membersindependently selected from the group consisting of lower alkyl,chloro-substituted lower alkyl, lower alkoxy, phenyl, and phenoxy; and Xis a member selected from the group consisting of oxygen and sulfur. 3.The compound having the formula ##STR31##
 6. The compound having theformula ##STR32##
 8. A compound having the formula: wherein R and R¹ areindependently selected lower alkyl groups and X is one of the chalcogensoxygen and
 9. The compound having the formula: ##STR33##
 10. Thecompound having the formula; ##STR34##11.
 11. The compound having theformula ##STR35##
 12. A compound having the formula: wherein R is loweralkoxy, R¹ is
 13. The compound according to claim 12 wherein R isethoxy, R¹ is
 14. The compound according to claim 12 wherein R isethoxy, R¹ is
 15. The compound according to claim 12 wherein R isiso-butoxy, R¹ is
 16. The compound according to claim 12 wherein R isiso-propoxy, R¹ is
 17. The compound according to claim 12 wherein R ismethoxy, R¹ is methyl and X is sulfur.